Preparation of 4-Methoxypropiophenone using Methanesulfonic Acid (MSA)

[William Dampier]

Reaction scheme:

Synthesis:

1. Methanesulfonic acid (MSA, 1920 g), propionic acid (23 g), and anisole (108 g) were charged into a 1-liter reaction flask.
2. The mixture was stirred for 8 hours at 45 °C.
3. After completion of the reaction, the reaction mass was diluted with water, and the product and unreacted anisole were extracted using toluene.
4. The toluene layer was distilled to recover 24 g of unreacted anisole and obtain 100 g of 4-Methoxypropiophenone.
5. The aqueous layer was distilled to recover 19 g of propionic acid and 1825 g of MSA, which was reused in subsequent batches.

Patent: US2022/0169588A1​

 

[fuzzypuma]

What is this precursor substance 4-Methoxypropiophenone used for?

 

[William Dampier]

This is more of an overview to familiarize oneself with what can be done with this method to make a more interesting 4-methylpropiophenone, for example. I tried synthesizing methedrone (from anisole) and I can’t say I liked the product. It’s weaker than analogs and significantly raises body temperature when consumed. However, the method of ketone production itself can be interesting, but it definitely requires refinement - patents always have errors so that the method cannot be simply replicated.